BASICS

Description

HL: B-cell neoplasm with low malignant cell burden (Reed-Sternberg cells) amid extensive inflammatory cells.
First described by Thomas Hodgkin (1832).
Two subtypes:
Classical HL (cHL): 95% cases; includes nodular sclerosing, mixed cellularity, lymphocyte rich, lymphocyte depleted.
Nodular lymphocyte predominant HL (NLPHL): 5%; characterized by "popcorn cells."

cHL arises from germinal center B cells with loss of B-cell markers.
Reed-Sternberg cells have clonal rearrangements with nonfunctional immunoglobulin genes.
Apoptosis escape through oncogenic events.
NLPHL has distinct "popcorn" large lymphocytic cells.
Genetic susceptibility linked to HLA alleles and familial risk.
EBV infection found in ~45% HL cases.
HIV infection increases HL risk.

HIV infection
EBV infection
Family history: 3–9x risk in first-degree relatives; 7x risk in siblings of young patients
Exposure to pesticides, herbicides, benzene (avoidance recommended)

Stage I: Single lymph node region or single extralymphatic site
Stage II: ≥2 lymph node regions on same side diaphragm (± extralymphatic)
Stage III: Nodes on both sides of diaphragm
Stage IV: Disseminated extranodal involvement (except spleen considered lymphoid)
Subclasses:
A: no systemic symptoms
B: systemic symptoms present
X: bulky disease (>1/3 intrathoracic diameter or >10 cm nodal mass)

Early stage: combined chemotherapy + radiotherapy
Advanced stage: chemotherapy alone
PET/CT after 2 cycles to guide treatment intensity
Chemotherapy regimens:
ABVD: doxorubicin, bleomycin, vinblastine, dacarbazine
- Monitor for phlebitis (central line recommended)
- Vinblastine: neuropathy risk
- Bleomycin: pulmonary toxicity (test dose recommended)
- Doxorubicin: cardiotoxicity (monitor LVEF)
AAVD: doxorubicin, brentuximab vedotin, vinblastine, dacarbazine
- Superior progression-free and overall survival vs ABVD (ECHELON-1 trial)
- Preferred in patients with abnormal pulmonary function
- Brentuximab vedotin side effects: neuropathy, neutropenia, fatigue, diarrhea

For relapsed/refractory disease:
Chemotherapy not previously used followed by high-dose therapy and autologous stem cell transplant (HDT/ASCT)
Immune checkpoint inhibitors:
- Pembrolizumab (anti-PD1), approved for ≥2 prior lines failure
- Nivolumab (anti-PD1), high overall response rate
Experimental therapies: bortezomib, everolimus, lenalidomide, CAR-T targeting CD30

CBC, nutrition, hydration during therapy
PET after 2 cycles for prognostic assessment
Post-treatment surveillance:
History and physical q3-6mo (2 years), then q6-12mo (1 year), then annually
Labs: CBC, platelets, BMP, ESR (if elevated initially), TSH annually if neck radiation
Imaging: PET-CT within 3 months post-treatment to confirm complete response; CT no more than every 6 months for 2 years or as clinically indicated
Annual mammogram starting 8–10 years post therapy or at 40 years (chest/axillary radiation)
Annual influenza vaccine
Cancer survivorship support and smoking cessation counseling

Peripheral neuropathy from treatment
Cardiovascular and valvular disease (anthracycline, radiation)
Bleomycin-induced irreversible pulmonary toxicity
Secondary malignancies: myeloid neoplasms (alkylating agents), breast cancer (radiation)

Barrington SF, Kirkwood AA, Franceschetto A, et al. PET-CT for staging and early response: results from the response-adapted therapy in advanced Hodgkin lymphoma study. Blood. 2016;127(12):1531-1538.
Ansell SM, Radford J, Connors JM, et al. Overall survival with brentuximab vedotin in stage III or IV Hodgkin's lymphoma. N Engl J Med. 2022;387(4):310-320.